Most physiological functions demonstrate periodicity with consistent and similar phase relationships in normal individuals. Altered phase relationships between functions may be a clue to the diagnosis and understanding of somatic and mental disease. The objectives of this program are to answer the following questions concerning the central mechanisms underlying circadian periodicity of pituitary-adrenal activity: 1) What is the location and mechanism of action of central structures which mediate diurnal variations in pituitary-adrenal function? Are these structures also involved in synchronizing the rhythm with the sleep-wake cycle and in diurnal modifications of the stress response? 2) How does the rhythm develop ontogenetically? Is the presence of the rhythm related to the maturation of a specific neural substrate? The effects of electrical stimulation of forebrain structures on basal levels of corticosteroids or ACTH will be studied in adult rats under diurnal lighting conditions. Sequential blood sampling via an indwelling catheter in freely-behaving chronically-implanted rats will permit definition of the nature of the effect on the diurnal rhythm, i.e. disruptive, obliterative or phase-shifted. These effects will be correlated with alterations in the spleen-wake cycle and in stress responsiveness. Neonatal hormonal treatment or ablations will be carried out in rats in order to study the developmental organization of the neural substrate for pituitary-adrenal rhythmicity. The effects of these neonatal treatments on the expression of the rhythm in adulthood will be correlated with effects on the sleep-wake cycle and stress responsiveness. Cyclic neuronal firing patterns in the localized structures will be recorded following these treatments in neonatal and adult rats.